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Synthesis and Antimicrobial Activity of some novel Formazan Derivatives

In the present investigation, a series of uracil formazans (5a-r) were synthesized by condensation of schiff base (4a-c) and diazonium salt of various substituted aromatic amines. The intermediate<br>schiff base (4a-c) was itself synthesized by condensation of (6-hydrazino-3-methyl uracil) with various aromatic aldehydes (3a-c). The structures of the compounds have been confirmed by elemental analysis and spectral analysis. Newly ynthesized compounds were screened for their antimicrobial activities. <br>

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Synthesis and Antimicrobial Activity of some novel Formazan Derivatives

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  1. Available on line www.jocpr.com Journal of Chemical and Pharmaceutical Research __________________________________________________ J. Chem. Pharm. Res., 2010, 2(4):60-67 ISSN No: 0975-7384 CODEN(USA): JCPRC5 Synthesis and Antimicrobial Activity of some novel Formazan Derivatives Amarish B. Samel and Nandini R. Pai* Department of Organic Chemistry, D.G. Ruparel College, Senapati Bapat Marg, Mahim, Mumbai-400 016, India ______________________________________________________________________________ ABSTRACT In the present investigation, a series of uracil formazans (5a-r) were synthesized by condensation of schiff base (4a-c) and diazonium salt of various substituted aromatic amines. The intermediate schiff base (4a-c) was itself synthesized by condensation of (6-hydrazino-3-methyl uracil) with various aromatic aldehydes (3a-c). The structures of the compounds have been confirmed by elemental analysis and spectral analysis. Newly synthesized compounds were screened for their antimicrobial activities. Keywords: Schiff base, Formazan, Antimicrobial activity. ______________________________________________________________________________ INTRODUCTION Formazans have been found to possess important medical applications; the tetrazolium salts are classified as promoter of vitality formazans and heterocyclic hydrazones are known for their spectrum of biological activities such as antiviral [1,2] antimicrobial [3], anti-inflammatory [4], antifungal [5], anticancer [6], anti-HIV [7-8], etc. Several formazans show promising anti- fertility [9] and anti-parkinsonian activity [10-13]. The importance of uracil and its annelated substrates is well recognized by synthetic as well as biological chemist, with the development of clinically useful anticancer (5-fluorouracil [14]) and antiviral drugs (AZT [15], BVDU [16, 17]). 6-(Arylazo) pyrimidine antimicrobials selectively inhibit replicative DNA synthesis in gram-positive bacteria by inhibiting, specifically, the replication-specific enzyme, DNA polymerase III [18-20]. 60

  2. Nandini R. Pai et al J. Chem. Pharm. Res., 2010, 2(4):60-67 _____________________________________________________________________________ In the present study we have synthesized eighteen substituted formazan derivatives (5a-r) by coupling Schiff base prepared from 6-hydrazino-3-methylpyrimidine-2,4(1H,3H)-dione (2) and various aldehydes (3a-c) with appropriate aryl diazonium chlorides in pyridine. (Scheme 1) The structures of these derivatives were assigned on the basis of elemental analysis, IR and 1H- NMR and antimicrobial activities. EXPERIMENTAL SECTION Melting points were determined in open capillaries on a Thomas Hoover apparatus and are uncorrected. 1H-NMR & 13C-NMR spectra were recorded on a Bruker AM 300 (300 MHz) instrument using tetramethylsilane (TMS) as an internal standard. Chemical shifts are given in parts per million (ppm). Splitting patterns are designated as follows: s- singlet, d- doublet, t- triplet, q- quartet and m- multiplet. Mass spectra (MS) were recorded on Shimadzu LC-MS. The reactions were followed on pre-coated TLC plates (Silica gel 60 F254, Merck), visualizing the spots in ultraviolet light. Scheme-1: 13C-NMR spectral data. The synthesized compounds were screened for their O O O N H2 N NH2 EtOH, r.t. O N N N EtOH, reflux N H O NH NH2 N H N N H O Cl OHC R R 3a-c 1 2 4a-c R = 3a -OMe 3b -Br 3c -Cl O R N 1. Pyrdine, CH3COONa N O N H N H N N 2. NaNO2, HCl, H2 N R' R' 5a-r Target compounds 5a-r were prepared according to Scheme-1 Reactionof .6-chloro-3- methylpyrimidine-2,4(1H,3H) dione with hydrazine hydrate afforded6-hydrazino-3-methy lpyrimidine-2,4(1H,3H)-dione (2) which was further condensed with para substituted benzaldehyde (3a-c) in presence of ethanol as a reaction medium gave schiff base (4a-c). Formation of schiff base (3a-c) was confirmed by appearance of IR band in the region 1650 cm-1 due to -N=CH- group, 1695 cm-1 due to >C=O group of amide, 3172 cm-1 due to -NH- group (secondary amine) of schiff base, 3 and disappearance of IR band in the region 3378 cm-1 & 1710 cm-1 corresponding to -NH2 group and -CHO group of 6-hydrazino-3-methylpyrimidine- 2,4(1H,3H)-dione (2) and para substituted benzaldehyde (3a-c) respectively. 1H-NMR spectra showed a singlet at δ 4.9 ppm due to -N=CH- (1H) of schiff base (4a-c) and disappearance of signal δ 9.9 ppm due to –CHO (1H) of para substituted benzaldehyde (3a-c). Similarly, 13C-NMR spectra showed a signal at δ 73.7 ppm due to -N=CH- of schiff base (4a-c). Further reaction of 61

  3. Nandini R. Pai et al J. Chem. Pharm. Res., 2010, 2(4):60-67 _____________________________________________________________________________ schiff base (4a-c) and diazonium salt of substituted aromatic amines in pyridine at 0-5 ºC afforded substituted formazans (5a-r). These compound show IR absorption band at 1600-1615 cm-1 due to –C=N- group, 1660-1724cm-1 due to >C=O group of amide, 3250-3300 cm-1 due to -NH- group (secondary amine) and 1508-1535 cm-1 due to -N=N group and the disappearance of bands at 1651 cm-1 (-N=CH-) also confirmed the formation of 5a-r. 1H-NMR spectra of formazans (5a-r) shows disappearance of singlet at δ 4.9 ppm due to -N=CH- of compound 4a-c. The synthetic route of above mentioned compounds is shown in Scheme-1. Table 1. Different substituent’s for R and R’ 5a-r Compounds R R’ 5a -OCH3 H 5b -OCH3 o-CH3 5c -OCH3o-OCH3 5d -OCH3m-OCH3 5e -OCH3p-OCH3 5f -OCH3 p-CL 5g -OCH3 m-Cl 5h -OCH3 p-F 5i -OCH3 m-F 5j -OCH3p-t-butyl 5k -Br o-CH3 5l -Br p-F 5m -Br m-F 5n -Br m-Cl 5o -Cl -H 5p -Cl o-CH3 5q -Cl m-OCH3 5r -Cl m-F Preparation of 6-hydrazino-3-methylpyrimidine-2,4(1H,3H)-dione(2) [21]: 6-chloro-3-methylpyrimidine-2,4(1H,3H)-dione (0.003mol) and Hydrazine hydrate (0.005 mol) were added to 4 ml of methoxy ethanol in a round bottom flask. The reaction mixture was heated to reflux for 20 minutes, cooled to room temperature and filtered. It was washed with ethanol and dried to get 6-hydrazino-3-methylpyrimidine-2,4(1H,3H)-dione in 64% yield mp:236-238ºC Preparation o f Benzyl(1-methyl-2,6-dioxo-1,2,3,6-tetrahydropyrimidin-4-yl)hydrazone (4a-c): A mixture of 6-hydrazino-3-methylpyrimidine-2,4(1H,3H)-dione (0.1 mol) and various para substituted benzaldehydes 3a-c (0.1 mol) in ethanol (20 mL) was stirred for 10 min at 25oC. After the completion of reaction it was poured into ice-cold water with stirring. The solid product obtained was filtered, washed with water and recrystallized from ethanol to get Benzyl(1-methyl- 2,6-dioxo-1,2,3,6-tetrahydropyrimidin-4-yl)hydrazone(4a-c). 4a. Yield (85%), mp 233oC [22]; IR: 3172 (NH),1298 (CN), 1695 (CO), 1651 (N=CH), 3107 & 1514 (aromatic ring, CH & C=C) cm-1. 1H-NMR (300 MHz;DMSO-d6): 3.05 (3H, s, NCH3), 4.90 (1H, s, N=CH), 6.78 (2H, d, J = 9 Hz), 7.03 (2H, d, J = 9 Hz), 7.14 (1H, s, C=CH-CO-), 10.82 (1H, s, NHCO), 10.89 (1H, s, HN-N=C); 13C-NMR (75.5 MHz; DMSO-d6): 26.1, 73.7, 113.9, 126.7, 128.8, 143.5, 150.0, 150.9, 160.5, 162.9. MP in °C 254 257 245 221 223 255 229 228 224 180 256 232 254 202 246 260 198 244 % Yield 66 64 61 60 63 62 65 63 60 76 74 73 73 71 65 63 61 62 62

  4. Nandini R. Pai et al J. Chem. Pharm. Res., 2010, 2(4):60-67 _____________________________________________________________________________ 4b. Yield (80%), mp 275oC; 1H-NMR (300 MHz;DMSO-d6): 3.08 (3H, s, NCH3), 4.91 (1H, s, N=CH), 7.57 (2H, d, J = 9 Hz), 7.83 (2H, d, J = 9 Hz), 7.93 (1H, s, C=CH-CO-), 11.01 (1H, s, NHCO), 11.18 (1H, s, HN-N=C); 13C-NMR (75.5 MHz; DMSO-d6): 24.6, 72.9, 121.2, 127.6, 129.9, 131.9, 140.7, 148.4, 149.4, 161.4. 4c. Yield (81%), mp 260oC [22]; 1H-NMR (300 MHz;DMSO-d6): 3.09 (3H, s, NCH3), 4.91 (1H, s, N=CH), 7.57 (2H, d, J = 9 Hz), 7.93 (2H, d, J = 9 Hz), 7.96 (1H, s, C=CH-CO-), 11.01 (1H, s, NHCO), 11.17 (1H, s, HN-N=C); 13C-NMR (75.5 MHz; DMSO-d6): 26.1, 74.4, 128.5, 128.9, 129.9, 142.1, 149.9, 150.9, 160.5, 162.9. Preparation of uracil formazans (5a-r) [23]: Substituted anilines (0.01 mole) were dissolved in aq. HCl (10 mL). It was cooled and aq. NaNO2 (0.7g) was slowly added. Benzyl (1-methyl-2,6-dioxo-1,2,3,6-tetrahydropyrimidin-4- yl)hydrazone (0.01 mole) was dissolved in dry pyridine (10 mL) and sodium acetate (0.3 g) was added. The contents were cooled in an ice-bath and stirred. To it a clear and cold solution of diazonium salt of substituted anilines was added drop wise for 1 hr at low temperature (0-5°C). The reaction mixture was kept in ice-bath for 5 min and then poured into ice water. The resulting dark coloured mass was collected by filtration, washed with water till it was free from pyridine and dried. The product was crystallized from ethanol. (5a-r). 5a. IR: 3265 (NH), 1724,1668 (>C=O of amide, C=O str.), 1608 (-N=C<, C=N str. in schiff base), 1519 (-N=N- str. in formazan), 1442 (C-N str.) cm-1; 1H-NMR (300 MHz; CDCl3):3.40 (3H, s, -N-CH3), 3.89 (3H, s, Ar -OCH3), 7.01- 7.81(9H, m, Ar-H) 8.46 (1H, s, C=CH), 9.35 (1H, s, NHCO), 14.88 (1H, s, HN-N=C); 13C-NMR (75.5 MHz; CDCl3): 27.8, 55.5, 114.5, 114.7, 116.6, 126.0, 126.1, 129.5, 130.5, 141.8, 147.0, 148.6, 158.9, 160.0, 162.7.; MS m/z:378. 5b. IR: 3265 (NH), 1724,1668 (>C=O of amide, C=O str.), 1608 (-N=C<, C=N str. in schiff base), 1519 (-N=N- str. in formazan), 1442 (C-N str.) cm-1; 1H-NMR (300 MHz; CDCl3):2.45 (3H, s, Ar-CH3),3.36 (3H, s, -N-CH3), 3.87 (3H, s, Ar -OCH3), 6.91- 7.99 (8H, m, Ar-H) 8.46 (1H, s,C=CH), 9.35 (1H, s, NHCO), 14.65 (1H, s, HN-N=C); 13C-NMR (75.5 MHz; CDCl3): 17.8, 27.8, 55.5, 114.5, 115.5, 115.8, 125.1, 125.8, 126.1, 127.7, 130.5, 130.7, 140.4, 147.1, 148.7, 158.4, 160.0, 162.7.; MS m/z:392. 5c. IR: 3265 (NH), 1718,1662 (>C=O of amide, C=O str.), 1612 (-N=C<, C=N str. in schiff base), 1514 (-N=N- str. in formazan), 1437 (C-N str.) cm-1; 1H-NMR(300 MHz; CDCl3):3.38 (3H, s, -N-CH3), 3.86 (3H, s, Ar -OCH3), 4.01 (3H, s, Ar -OCH3), 6.94- 7.97 (8H, m, Ar-H), 8.46 (1H, s,C=CH), 9.32 (1H, s, NHCO), 15.09 (1H, s, HN-N=C); 13C-NMR (75.5 MHz; CDCl3): 27.7, 55.5, 56.0, 110.9, 114.2, 114.5, 115.8, 121.8, 126.2, 130.1, 130.4, 146.5, 148.4, 148.7, 159.1, 160.3, 161.1, 162.6; MS m/z:408. 5d. IR: 3267 (NH), 1722,1664 (>C=O of amide, C=O str.), 1605 (-N=C<, C=N str. in schiff base), 1512 (-N=N- str. in formazan), 1442 (C-N str.) cm-1; 1H-NMR(300 MHz; CDCl3):3.33 (3H, s, -N-CH3), 3.81 (6H, s, Ar -OCH3), 6.67- 7.74 (8H, m, Ar-H), 8.38 (1H, s,C=CH), 9.28 (1H, s, NHCO), 14.79 (1H, s, HN-N=C); 13C-NMR (75.5 MHz; CDCl3): 27.7, 55.5, 55.6, 101.6, 109.3, 112.1, 114.3, 114.5, 126.1, 130.2, 130.5, 143.1, 146.9, 148.6, 158.9, 160.0, 160.9, 162.7.; MS m/z:408. 5e. IR: 3267 (NH), 1720,1664 (>C=O of amide, C=O str.), 1606 (-N=C<, C=N str. in schiff base), 1512 (-N=N- str. in formazan), 1440 (C-N str.) cm-1; 1H-NMR(300 MHz; CDCl3):3.26 (3H, s, -N-CH3), 3.74 (3H, s, Ar -OCH3), 3.78 (3H, s, Ar -OCH3), 6.83- 7.69 (8H, m, Ar-H), 8.31 (1H, s,C=CH), 9.24 (1H, s, NHCO), 14.89 (1H, s, HN-N=C); 13C-NMR (75.5 MHz; CDCl3): 27.6, 55.4, 55.5, 113.7, 114.4, 114.8, 117.9, 126.2, 130.4, 135.4, 147.1, 148.7, 158.1, 158.3, 160.1, 162.5.; MS m/z:408. 5f. IR: 3265 (NH), 1724,1668 (>C=O of amide, C=O str.), 1608 (-N=C<, C=N str. in schiff base), 1519 (-N=N- str. in formazan), 1442 (C-N str.) cm-1; 1H-NMR (300 MHz; CDCl3):3.40 63

  5. Nandini R. Pai et al J. Chem. Pharm. Res., 2010, 2(4):60-67 _____________________________________________________________________________ (3H, s, -N-CH3), 3.89 (3H, s, Ar -OCH3), 6.98- 7.80 (8H, m, Ar-H), 8.45 (1H, s,C=CH), 9.35 (1H, s, NHCO), 14.91 (1H, s, HN-N=C); 13C-NMR (75.5 MHz; CDCl3): 27.8, 55.5, 114.5, 116.3, 116.6, 118.0, 118.1, 126.1, 130.5, 138.1, 147.0, 148.6, 158.9, 160.0, 162.8, ; MS m/z: 396. 5g. IR: 3265 (NH), 1724,1668 (>C=O of amide, C=O str.), 1608 (-N=C<, C=N str. in schiff base), 1519 (-N=N- str. in formazan), 1442 (C-N str.) cm-1; 1H-NMR (300 MHz; CDCl3):3.41 (3H, s, -N-CH3), 3.90 (3H, s, Ar -OCH3), 6.98- 7.71 (8H, m, Ar-H), 8.47 (1H, s,C=CH), 9.34 (1H, s, NHCO), 14.79 (1H, s, HN-N=C); 13C-NMR (75.5 MHz; CDCl3): 27.8, 55.5, 114.5, 114.6, 115.6, 116.5, 118.0,118.2, 126.0, 130.5, 130.6, 138.1,146.8, 148.5, 158.8, 160.1, 162.8.; MS m/z:396 5h. IR: 3257 (NH), 1724,1668 (>C=O of amide, C=O str.), 1606 (-N=C<, C=N str. in schiff base), 1514 (-N=N- str. in formazan), 1442 (C-N str.) cm-1; 1H-NMR (300 MHz; CDCl3):3.32 (3H, s, -N-CH3), 3.82 (3H, s, Ar -OCH3), 6.91- 7.73 (8H, m, Ar-H), 8.38 (1H, s,C=CH), 9.27 (1H, s, NHCO), 14.78 (1H, s, HN-N=C); 13C-NMR (75.5 MHz; CDCl3): 26.8, 54.5, 113.5, 114.2, 116.6, 125.0, 128.6, 129.6, 130.1, 139.4, 145.9, 147.5, 158.1, 158.8, 161.8.; MS m/z:412 5i. IR: 3263 (NH), 1722,1668 (>C=O of amide, C=O str.), 1606 (-N=C<, C=N str. in schiff base), 1514 (-N=N- str. in formazan), 1440 (C-N str.) cm-1; 1H-NMR (300 MHz; CDCl3):3.39 (3H, s, -N-CH3), 3.90 (3H, s, Ar -OCH3), 6.98- 7.81 (8H, m, Ar-H), 8.43 (1H, s,C=CH), 9.36 (1H, s, NHCO), 14.79 (1H, s, HN-N=C); 13C-NMR (75.5 MHz; CDCl3): 27.8, 55.5, 114.5, 114.6, 115.6, 116.5, 125.7, 126.0, 130.5, 130.6, 135.5, 143.0, 146.8, 148.5, 159.4, 159.7, 162.8.; MS m/z:412 5j. IR: 3265 (NH), 1722,1668 (>C=O of amide, C=O str.), 1606 (-N=C<, C=N str. in schiff base), 1512 (-N=N- str. in formazan), 1438 (C-N str.) cm-1; 1H-NMR (300 MHz; CDCl3):1.33 (9H, s, -C(CH3)3),3.38 (3H, s, -N-CH3), 3.88 (3H, s, Ar -OCH3), 3.78 (3H, s, Ar -OCH3), 6.97- 7.80 (8H, m, Ar-H), 8.44 (1H, s,C=CH), 9.36 (1H, s, NHCO), 14.92 (1H, s, HN-N=C); 13C- NMR (75.5 MHz; CDCl3): 27.7, 31.3, 34.6, 55.5, 114.2, 114.5, 116.3, 126.2, 126.4, 130.4, 139.4, 147.1, 148.7, 149.5, 158.6, 160.1, 162.6.; MS m/z:434. 5k. IR: 3261 (NH), 1722,1670 (>C=O of amide, C=O str.), 1612 (-N=C<, C=N str. in schiff base), 1535 (-N=N- str. in formazan), 1431 (C-N str.) cm-1; 1H-NMR (300 MHz; CDCl3):2.48 (3H, s, Ar-CH3),3.41 (3H, s, -N-CH3), 7.12- 7.99 (8H, m, Ar-H) 8.42 (1H, s,C=CH), 9.32 (1H, s, NHCO), 14.61 (1H, s, HN-N=C); 13C-NMR (75.5 MHz; CDCl3): 17.8, 27.8, 115.2, 115.9, 125.2, 126.1, 126.5, 127.7, 129.9,130.8, 132.3, 140.2, 148.1, 148.5, 157.5, 159.9.; MS m/z:441. 5l. IR: 3265 (NH), 1724,1668 (>C=O of amide, C=O str.), 1608 (-N=C<, C=N str. in schiff base), 1519 (-N=N- str. in formazan), 1442 (C-N str.) cm-1; 1H-NMR (300 MHz; CDCl3):3.34 (3H, s, -N-CH3), 7.03- 7.65 (8H, m, Ar-H) 8.40 (1H, s,C=CH), 9.27 (1H, s, NHCO), 14.80 (1H, s, HN-N=C); 13C-NMR (75.5 MHz; CDCl3): 29.6, 116.4, 116.7,118.1, 118.2, 126.5, 129.9, 132.2, 132.3, 136.6, 139.2, 147.9, 148.5, 158.1.; MS m/z:445 5m. IR: 3265 (NH), 1722,1670 (>C=O of amide, C=O str.), 1612 (-N=C<, C=N str. in schiff base), 1531 (-N=N- str. in formazan), 1436 (C-N str.) cm-1; 1H-NMR (300 MHz; CDCl3):3.41 (3H, s, -N-CH3), 6.88- 7.73 (8H, m, Ar-H) 8.48 (1H, s,C=CH), 9.32 (1H, s, NHCO), 14.76 (1H, s, HN-N=C); 13C-NMR (75.5 MHz; CDCl3): 27.9, 103.7, 112.3, 112.8, 113.0, 115.2, 126.7, 130.0,130.8, 132.2, 132.4, 143.3, 143.7, 147.9, 148.5, 158.8; MS m/z:445. 5n. IR: 3244 (NH), 1724,1672 (>C=O of amide, C=O str.), 1612 (-N=C<, C=N str. in schiff base), 1533 (-N=N- str. in formazan), 1454 (C-N str.) cm-1; 1H-NMR (300 MHz; CDCl3):3.34 (3H, s, -N-CH3), 6.84- 7.67 (8H, m, Ar-H) 8.42 (1H, s,C=CH), 9.24 (1H, s, NHCO), 14.76 (1H, s, HN-N=C); 13C-NMR (75.5 MHz; CDCl3): 29.6, 114.7, 115.3, 116.6, 125.8, 126.0, 129.9, 130.0, 132.1, 132.4, 132.8, 142.7, 147.7, 148.4, 158.6, 161.1.; MS m/z:461 64

  6. Nandini R. Pai et al J. Chem. Pharm. Res., 2010, 2(4):60-67 _____________________________________________________________________________ 5o. IR: 3265 (NH), 1724,1668 (>C=O of amide, C=O str.), 1608 (-N=C<, C=N str. in schiff base), 1519 (-N=N- str. in formazan), 1442 (C-N str.) cm-1; 1H-NMR (300 MHz; CDCl3):3.33 (3H, s, -N-CH3), 7.13- 7.73 (8H, m, Ar-H) 8.42 (1H, s,C=CH), 9.25 (1H, s, NHCO), 14.76 (1H, s, HN-N=C); 13C-NMR (75.5 MHz; CDCl3): 27.6, 114.3, 116.5, 126.1, 129.2, 129.4, 129.6, 131.7, 137.8, 141.4, 147.7, 148.3, 157.8, 159.7.; MS m/z:382. 5p. IR: 3265 (NH), 1724,1668 (>C=O of amide, C=O str.), 1608 (-N=C<, C=N str. in schiff base), 1519 (-N=N- str. in formazan), 1442 (C-N str.) cm-1; 1H-NMR (300 MHz; CDCl3):2.49 (3H, s, Ar-CH3),3.42 (3H, s, -N-CH3), 7.11- 7.99 (8H, m, Ar-H) 8.44 (1H, s,C=CH), 9.32 (1H, s, NHCO), 14.62 (1H, s, HN-N=C); 13C-NMR (75.5 MHz; CDCl3): 17.8, 27.8, 115.2, 115.9, 125.2, 126.1, 127.7, 129.3, 129.8, 130.8, 131.9, 138.0, 140.2, 148.0, 148.5, 157.5, 159.9.; MS m/z:396 5q. IR: 3246 (NH), 1724,1668 (>C=O of amide, C=O str.), 1612 (-N=C<, C=N str. in schiff base), 1535 (-N=N- str. in formazan), 1442 (C-N str.) cm-1; 1H-NMR (300 MHz; CDCl3):3.40 (3H, s, -N-CH3), 3.88 (3H, s, Ar -OCH3), 6.74- 7.79 (8H, m, Ar-H), 8.47 (1H, s,C=CH), 9.31 (1H, s, NHCO), 14.78 (1H, s, HN-N=C); 13C-NMR (75.5 MHz; CDCl3): 25.7, 53.5, 99.7, 107.3, 110.2, 112.4, 127.3, 127.7, 128.2, 129.8, 136.0, 140.8, 145.8, 146.5, 156.0, 157.8, 159.0.; MS m/z:412 5r. IR: 3253 (NH), 1722,1666 (>C=O of amide, C=O str.), 1612 (-N=C<, C=N str. in schiff base), 1531 (-N=N- str. in formazan), 1435 (C-N str.) cm-1; 1H-NMR (300 MHz;CDCl3):3.33 (3H, s, -N-CH3), 6.81- 7.73 (8H, m, Ar-H) 8.42 (1H, s,C=CH), 9.24 (1H, s, NHCO), 14.69 (1H, s, HN-N=C); 13C-NMR (75.5 MHz; CDCl3): 26.8, 103.1, 111.3, 111.8, 112.0, 114.2, 128.4, 128.8, 129.9, 130.7, 137.1, 142.4, 146.7, 147.3, 157.4, 158.5 ; MS m/z:400. Table 2: Antimicrobial activity of compounds, zone of inhibition in mm. Compounds E.coli (-) S.aureus(+) 5a 4.1 2.2 5b 3.8 3.7 5c 9.4 4.6 5d 3.5 3.0 5e 4.1 4.2 5f 4.0 3.9 5g 3.2 3.1 5h 2.8 2.9 5i 3.2 2.5 5j 4.2 4.1 5k 5.1 9.6 5l 2.8 2.8 5m 2.1 2.3 5n 8.5 4.2 5o 6.2 13.9 5p 5.1 8.3 5q 3.5 3.5 5r 2.1 2.3 GENTAMICIN 16.2 14.3 MICONAZOLE - - S.cerevisiae 8.2 4.5 7.2 2.0 4.2 4.6 2.9 2.8 6.3 10.5 2.1 2.9 2.8 2.2 2.1 2.4 2.3 7.2 - 11.5 C.albicans 5.0 12.8 3.4 2.0 11.2 12.6 2.8 1.8 2.5 8.8 2.6 3.0 2.7 2.2 2.3 2.8 2.0 3.3 - 13.2 65

  7. Nandini R. Pai et al J. Chem. Pharm. Res., 2010, 2(4):60-67 _____________________________________________________________________________ Antimicrobial activity The synthesized compounds 5a-r were screened for their antibacterial activity against E. Coli and S.Aureus and antifungal activity against S.Cerevisiae and C.albicans at a concentration of 60 µg/mL in DMF by cup-plate method [24, 25]. Standard anti-bacterial and antifungal drug, gentamycin and miconazole respectively were also tested under similar conditions for comparison. Zone of inhibition in mm of synthesized compounds and standard drugs are shown in Table 2. CONCLUSION A series of novel uracil formazans (5a-r) were synthesized, the structures of the compounds have been confirmed by elemental analysis and spectral analysis. Most of the synthesized compounds have shown antibacterial and antifungal activity to some extent. Among the synthesized compounds, 5c and 5n show some activity, while rest show feeble activity against E. coli. Against S.Aureus the compound 5o shows good activity, while compounds 5k and 5p show moderate activity. The remaining compounds have been found to be less active against S.Aureus. The compound 5j shows good activity, while compounds 5a, 5c, 5i, and 5r show moderate activity against S.Cerevisiaec The compounds 5b and 5f show good activity while compounds 5e and 5j show moderate to good activity against C. albicans. Acknowledgements: The authors are thankful to BASF India Ltd. for providing analytical support. REFERENCES [1]V.K.Pandey and H.S.Negi, Indian Drugs (Indian Drug Manufacturers Association), 1999, 36(1), 37. [2]V S Mishra, S Dhar and B L Chowdhary, Pharmazie, 1978, 33, 790 [3]R M Desai and J M Desai, Indian J Heterocycl Chem., 1999, 8(4), 329 [4]H G Garg and M, J Kaur Med Chem., 1992, 15, 554. [5]K G Desai and K R Desai, Indian J Chem., 2005, 44(B), 2097. [6]S D Bhardwaj, P Phatak and V S Jolly, Orient J Chem., 1995, 2, 181. [7]N K Venkal, J Med Chem., 1998, 8, 11. [8]S D Bhardwaj and V S, Jolly Asian J Chem., 1997, 9, 48. [9]J M Desai and V H Shah, Indian J Chem., 2003,42(B), 631. [10]R.Khanna, A.K.Saxena, V.K.Srivastava and K.Shanker, Indian J Chem., 1990,29(B), 91. [11]P.Kumar, C.Nath, J.C.Agarwal, K.P.Bhargava and K.Shanker, Indian J Chem., 1983,22(B), 955. [12]Naithani P K, Srivastava V K, Barthwal J P, Saxena A K, Gupta T K and Shanker K,Indian J Chem., 1989, 28(B), 990. [13]P.Kumar, C.Nath and K.Shanker, Pharmazie, 1985, 40, 267. [14]C.Heidelberger, F. J. Arafield, Cancer Res. 1963,23,1226;Chem.Abstr. 1964, 60, 2197. [15]E. D. Clercq, J. Med. Chem. 1986, 29, 1561. [16]E. D. Clercq, Anticancer Res. 1986, 6, 549. [17]S. Jones, G.Verhalst, R. T. Walker, Tetrahedron Lett. 1974, 4415. [18]M. M. Neville and N. C. Brown, Nature (London), New Biol., 240, 80 (1972). [19]G. W. Bazill and J. D. Gross, Nature (London), New Biol., 240, 82 (1972). [20]K. B. Gass, R. L. Low, and N. R. Cozzarelli, Proc. Natl. Acad. Sci. U.S.A., 70, 103 (1973). [21]T. K.Liao, F.Baiocch, C. C. Cheng J. Organic chem.1966, 31, 900-902 66

  8. Nandini R. Pai et al J. Chem. Pharm. Res., 2010, 2(4):60-67 _____________________________________________________________________________ [22]F. Yoneda, T. Nagamatsu Synthesis1973, 5, 300-01. [23]Raval et al, International Journal of Pharmaceutical Research 2009, 1, 62-71. [24]L. Banty, The Antimicrobial Susceptibility test; Principle and practice, Edited by Illus lea and Febiger, (Philadelphia, Pa USA), 1976, 180. [25]H .W. Seely and P. J. Van Demark, Microbes in action: A laboratory manual of Microbiology, D B Taraporewala Sons and Co, Bombay, 1975, 55-80. 67

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